N-acetylcysteine (NAC) is a well-known drug approved worldwide for several indications mainly as mucolytic agent but it is also one of the few available treatments for acetaminophen poisoning.
Acetaminophen (paracetamol) is a commonly used analgesic and antipyretic drug. Accidental or suicidal acetaminophen overdose can cause severe liver damage which result in several deaths each year in the U.S.A.
NAC is effective by intravenous or oral route for the treatment of acetaminophen poisoning if administered within 8-10 hours of acetaminophen overdose. The dose of NAC to be administered is very high according to the Prescott therapy protocol, as reported in the following table 1:
TABLE 1NAC doses according to the Prescott therapy protocolNACNACBody weightloading dosemaintenance dose(kg)(g)(g)100-109157.590-9914780-89136.570-79115.560-6910550-598440-4973.530-396320-2942
The only available NAC dosage form for the treatment of acetaminophen poisoning is Acetadote®, 30 ml vials containing 200 mg/ml NAC for intravenous administration.
The oral treatment of acetaminophen poisoning with NAC is equally or even more effective than intravenous treatment when administered within 8-10 hours of acetaminophen overdose (Michele Zell Kanter, American Journal of Health—System Pharmacy, Oct. 1, 2006 vol. 63 no. 19, 1821-1827), the contents of which are incorporated herein by reference and would be more practical and safer. However, the very high dosage limits the possibility to use commercially available NAC formulations for oral administration which usually have a maximum NAC content of 600 mg.
Therefore, it would be desirable to have an oral formulation containing a high amount of NAC to be used for the treatment of acetaminophen poisoning.